The objective is to obtain new information on the structure and function of fibrinogen. The primary structure of the disulfide containing peptides from CNBr treated fibrinogen is studied because these regions are crucial for the precise holding of the chains. The structure of the N-DSK, containing 11 out of the 28 disulfides in fibrinogen, is virtually completed; the other disulfide fragments are under investigation. Sequencing of the NH2-terminal regions of plasmic Fragment D and of overlapping peptides (CNBr derived) between Fragments D and E will allow further elucidation of the primary structure of fibrinogen. The three-dimensional structure of fibrinogen will be studied by determining surface oriented antigens with the use of specific antibodies in radioimmune systems and thioredoxin reductase sensitive disulfides. The structures in fibrinogen involved in the fibrin formation are being investigated by studying the binding of chemically and enzymatically derived fragments of fibrinogen to insolubilized fibrin monomer. Such knowledge is fundamental for the design of specific anticoagulants. The role of disulfide exchange in the crosslinking of fibrin is investigated by studying the structure of polymers obtained by reoxidation of thioredoxin reductase reduced fibrinogen. In addition the thioredoxin-like substance in human platelets will be isolated and thioreductase-like activity in different organs determined. Radioimmunoassay for fibrinogen and its chains will provide us with a tool for the study of fibrinogen biosynthesis. The specificity binding to alpha 2-macroglobulin and metabolism of Reptilase are studied to evaluate its therapeutic usefulness. New rapid methods for the determination of coagulation factors and their inhibitors will be devised with the use of synthetic thrombin substrate benzoyl-Phe-Val-Arg-p-nitroanilide.